Analyte sensors and sensing methods for detecting creatinine

Inventors

Ouyang, Tianmei • Feldman, Benjamin J. • Cho, Hyun

Assignees

Abbott Diabetes Care Inc

Abstract

Creatinine levels may be monitored as a measure of kidney function. Conventionally, blood and/or urine tests are used for this purpose. Analyte sensors capable of monitoring creatinine in vivo may comprise: a sensor tail comprising at least a first working electrode, a creatinine-responsive active area disposed upon a surface of the first working electrode, a first membrane that is permeable to creatinine and overcoats the creatinine-responsive active area, and an oxygen scavenger located upon the sensor tail in proximity to the creatinine-responsive active area. The creatinine-responsive active area comprises a first electron transfer agent, a first polymer, and an enzyme system comprising multiple enzymes, particularly creatinine amidohydrolase, creatine amidinohydrolase, and sarcosine oxidase, that are capable of acting in concert to facilitate detection of creatinine. An oxidase enzyme may serve as the oxygen scavenger, particularly glucose oxidase when detecting creatinine in fluids also containing glucose.

Core Innovation

The invention provides an analyte sensor that detects creatinine in vivo by using a creatinine-responsive active area disposed on a distal end of a first working electrode. The creatinine-responsive active area includes an electron transfer agent, a first polymer, and an enzyme system comprising creatinine amidohydrolase, creatine amidinohydrolase, and sarcosine oxidase. The sensor includes a dielectric layer covering the first working electrode other than the distal end and a first membrane permeable to creatinine that overcoats the creatinine-responsive active area.

To mitigate oxygen interference, the sensor includes an area for oxygen scavenging disposed upon the first membrane and isolated from the first working electrode. The oxygen scavenging area comprises glucose oxidase as an oxygen scavenger. This oxygen scavenging region is structurally separated from the working electrode and arranged upon the membrane, while the creatinine-responsive active area remains at the distal end for contact with interstitial fluid.

In one embodiment, the sensor further includes a second working electrode with a glucose-responsive active area on a surface of the second working electrode. The glucose-responsive active area comprises a second electron transfer agent, a third polymer, and glucose oxidase covalently bonded to the third polymer, and it is overcoated by a second membrane permeable to glucose. The sensor is configured to be partially inserted into a tissue such that a distal portion contacts interstitial fluid to detect both glucose and creatinine in vivo.

Claims Coverage

The partial content includes two independent claims: an analyte sensor for in vivo creatinine detection using a creatinine-responsive electrochemical active area and oxygen scavenging, and a dual-analyte sensor configured for in vivo glucose and creatinine detection using separate working electrodes and corresponding membrane-covered active areas. Across the independent claims, at least two main inventive features are combined in each: a multi-enzyme creatinine cascade active area with an electron transfer agent and polymer, and an oxygen-scavenging region using glucose oxidase isolated from the working electrode, with optional glucose-responsive detection in the second independent claim.

The independent claims cover an in vivo creatinine electrochemical sensor that uses a distal creatinine-responsive active area with a multi-enzyme system and an electron transfer agent, while oxygen interference is addressed by an oxygen-scavenging region comprising glucose oxidase isolated from the working electrode. A second independent claim adds a second working electrode with a glucose-responsive active area and a glucose-permeable membrane, enabling in vivo detection of glucose and creatinine.

Stated Advantages

Documented Applications

No documented applications found